tbuckley/cabot-search huggingface dataset:
Evaluation of Socioeconomic Position and Survival After Out-of-Hospital Cardiac Arrest in Korea Using Structural Equation Modeling
Authors: Dong Hyun Choi, Young Sun Ro, Jeong Ho Park, Sun Young Lee, Ki Jeong Hong, Kyoung Jun Song, Sang Do Shin
Journal: JAMA Network Open (2023)

Importance The association between low socioeconomic position (SEP) and poor survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. Objectives To evaluate the association between individual SEP and survival after OHCA and to identify any mediating pathways using structural equation modeling (SEM). Design, Setting, and Participants This is a retrospective cohort study that used data collected from January 2013 to December 2019. Participants were adults with OHCA with a presumed cardiac etiology. The study was conducted in Korea, which has a universal health insurance system. Data were analyzed from January 2022 to February 2023. Exposures Individual SEP was measured by insurance type (National Health Insurance [NHI] and medical aid [MA]) and premiums. SEP was categorized into 5 groups, in which NHI beneficiaries were divided into quartiles (Q1, highest quartile; Q4, lowest quartile), and MA was the lowest SEP group. Main Outcomes and Measures The primary outcome was survival to discharge. The association between SEP and OHCA survival was examined using multivariable logistic regression, and mediating factors were identified using SEM. Results A total of 121 516 patients (median [IQR] age, 73 [60-81] years; 43 912 [36.1%] female patients) were included. Compared with the NHI Q1 group, individuals with lower SEP had lower odds of survival to discharge. The adjusted odds ratios of survival to discharge were 0.97 (95% CI, 0.94-1.00), 0.88 (95% CI, 0.85-0.91), 0.91 (95% CI, 0.88-0.94), and 0.53 (95% CI, 0.50-0.56) for the NHI Q2, NHI Q3, NHI Q4, and MA groups, respectively. Several factors were found to mediate the association of SEP and survival in the total study population, with mediating proportions of 15.1% (95% CI, 11.8%-18.4%) for witnessed status, 4.8% (95% CI, 3.5%-6.0%) for bystander cardiopulmonary resuscitation provision, 41.8% (95% CI, 35.4%-48.1%) for initial rhythm, and 9.4% (95% CI, 7.4%-11.4%) for emergency department level. Among patients who survived to hospital admission, the mediation proportions were 11.8% (95% CI, 6.7%-16.9%) for witnessed status, 3.7% (95% CI, 1.3%-6.1%) for bystander cardiopulmonary resuscitation provision, 56.2% (95% CI, 41.0%-71.4%) for initial rhythm, 10.7% (95% CI, 6.1%-15.3%) for emergency department level, 20.2% (95% CI, 14.0%-26.5%) for coronary angiography, and 4.2% (95% CI, 2.2%-6.1%) for targeted temperature management. Conclusions and Relevance In this cohort study of patients with OHCA, lower individual SEP was significantly associated with lower survival to discharge. Potentially modifiable mediators can be targeted for public health interventions to reduce disparities in survival among patients with OHCA of different SEP.
Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis
Authors: Máté G. Kiss, John E. Mindur, Abi G. Yates, Donghoon Lee, John F. Fullard, Atsushi Anzai, Wolfram C. Poller, Kathleen A. Christie, Yoshiko Iwamoto, Vladimir Roudko, Jeffrey Downey, Christopher T. Chan, Pacific Huynh, Henrike Janssen, Achilles Ntranos, Jan D. Hoffmann, Walter Jacob, Sukanya Goswami, Sumnima Singh, David Leppert, Jens Kuhle, Seunghee Kim-Schulze, Matthias Nahrendorf, Benjamin P. Kleinstiver, Fay Probert, Panos Roussos, Filip K. Swirski, Cameron S. McAlpine
Journal: Immunity (2023)
Identifying Barriers to OUD Treatment Linkage From the Emergency Department to the Community
Authors: Susan L. Calcaterra, Marlene Martin, Honora Englander
Journal: JAMA Network Open (2023)

Kimberly L. Sue, MD, PhD; Marek Chawarski, PhD; Leslie Curry, PhD, MPH; Ryan McNeil, PhD; Edouard Coupet Jr, MD, MS; Robert P. Schwartz, MD; Christine Wilder, MD, MHES; Judith I. Tsui, MD, MPH; Kathryn F. Hawk, MD, MHS; Gail D'Onofrio, MD, MS; Patrick G. O'Connor, MD, MPH; David A. Fiellin, MD; E. Jennifer Edelman, MD, MHS
Engineering highly thermostable Cas12b via de novo structural analyses for one-pot detection of nucleic acids
Authors: Long T. Nguyen, Santosh R. Rananaware, Lilia G. Yang, Nicolas C. Macaluso, Julio E. Ocana-Ortiz, Katelyn S. Meister, Brianna L.M. Pizzano, Luke Samuel W. Sandoval, Raymond C. Hautamaki, Zoe R. Fang, Sara M. Joseph, Grace M. Shoemaker, Dylan R. Carman, Liwei Chang, Noah R. Rakestraw, Jon F. Zachary, Sebastian Guerra, Alberto Perez, Piyush K. Jain
Journal: Cell Reports Medicine (2023)

CRISPR-Cas-based diagnostics have the potential to elevate nucleic acid detection. CRISPR-Cas systems can be combined with a pre-amplification step in a one-pot reaction to simplify the workflow and reduce carryover contamination. Here, we report an engineered Cas12b with improved thermostability that falls within the optimal temperature range (60°C–65°C) of reverse transcription-loop-mediated isothermal amplification (RT-LAMP). Using de novo structural analyses, we introduce mutations to wild-type BrCas12b to tighten its hydrophobic cores, thereby enhancing thermostability. The one-pot detection assay utilizing the engineered BrCas12b, called SPLENDID (single-pot LAMP-mediated engineered BrCas12b for nucleic acid detection of infectious diseases), exhibits robust trans-cleavage activity up to 67°C in a one-pot setting. We validate SPLENDID clinically in 80 serum samples for hepatitis C virus (HCV) and 66 saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and accuracy. We obtain results in as little as 20 min, and with the extraction process, the entire assay can be performed within an hour.
Is the Scale of Alopecia Areata Distress a new method of assessing the psychological burden of alopecia areata?
Authors: Taisuke Ito, Reiko Kageyama
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Is the Scale of Alopecia Areata Distress a new method of assessing the psychological burden of alopecia areata? Get access Taisuke Ito, Taisuke Ito Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Correspondence: Taisuke Ito. Email: itoutai@hama-med.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Reiko Kageyama Reiko Kageyama Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad153, https://doi.org/10.1093/bjd/ljad153 Published: 10 May 2023 Article history Received: 20 April 2023 Revision received: 27 April 2023 Accepted: 28 April 2023 Published: 10 May 2023 Corrected and typeset: 14 June 2023
Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension
Authors: Mazher Mohammed, Blessing Ogunlade, Mona Elgazzaz, Clara Berdasco, Navya Lakkappa, Ioana Ghita, Jessie J Guidry, Srinivas Sriramula, Jiaxi Xu, Luke Restivo, Michelle A Mendiola Plá, Dawn E Bowles, Andreas M Beyer, Xinping Yue, Eric Lazartigues, Catalin M Filipeanu
Journal: Cardiovascular Research (2023)

Abstract Aims Angiotensin-converting enzyme 2 (ACE2) is a critical component of the compensatory renin–angiotensin system that is down-regulated during the development of hypertension, possibly via ubiquitination. However, little is known about the mechanisms involved in ACE2 ubiquitination in neurogenic hypertension. This study aimed at identifying ACE2 ubiquitination partners, establishing causal relationships and clinical relevance, and testing a gene therapy strategy to mitigate ACE2 ubiquitination in neurogenic hypertension. Methods and results Bioinformatics and proteomics were combined to identify E3 ubiquitin ligases associated with ACE2 ubiquitination in chronically hypertensive mice. In vitro gain/loss of function experiments assessed ACE2 expression and activity to validate the interaction between ACE2 and the identified E3 ligase. Mutation experiments were further used to generate a ubiquitination-resistant ACE2 mutant (ACE2-5R). Optogenetics, blood pressure telemetry, pharmacological blockade of GABAA receptors in mice expressing ACE2-5R in the bed nucleus of the stria terminalis (BNST), and capillary western analysis were used to assess the role of ACE2 ubiquitination in neurogenic hypertension. Ubiquitination was first validated as leading to ACE2 down-regulation, and Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) was identified as a E3 ligase up-regulated in hypertension and promoting ACE2 ubiquitination. Mutation of lysine residues in the C-terminal of ACE2 was associated with increased activity and resistance to angiotensin (Ang)-II-mediated degradation. Mice transfected with ACE2-5R in the BNST exhibited enhanced GABAergic input to the paraventricular nucleus (PVN) and a reduction in hypertension. ACE2-5R expression was associated with reduced Nedd4-2 levels in the BNST. Conclusion Our data identify Nedd4-2 as the first E3 ubiquitin ligase involved in ACE2 ubiquitination in Ang-II-mediated hypertension. We demonstrate the pivotal role of ACE2 on GABAergic neurons in the maintenance of an inhibitory tone to the PVN and the regulation of pre-sympathetic activity. These findings provide a new working model where Nedd4-2 could contribute to ACE2 ubiquitination, leading to the development of neurogenic hypertension and highlighting potential novel therapeutic strategies.
Preclinical Development and Validation of Translational Temperature Sensitive Iodized Oil Emulsion Mediated Transcatheter Arterial Chemo‐Immuno‐Embolization for the Treatment of Hepatocellular Carcinoma
Authors: Heegon Kim, Bongseo Choi, Samdeep K. Mouli, Hyunjun Choi, Kathleen R. Harris, Laura M. Kulik, Robert J. Lewandowski, Dong‐Hyun Kim
Journal: Advanced Healthcare Materials (2023)

Herein a practical strategy for augmenting immune activation in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) is presented. Pluronic F127 (PF127) is incorporated with Lipiodol (LPD) to achieve safe and effective delivery of therapeutic agents during transcatheter intra-arterial (IA) local delivery. Enhanced emulsion stability, IA infusion, embolic effect, safety, pharmacokinetics, and tumor response of Doxorubicin loaded PF127-LPD (Dox-PF127-LPD) for TACE in both in vitro and in vivo preclinical VX2 liver cancer rabbit model and N1S1 HCC rat model are demonstrated. Then, transcatheter arterial chemo-immuno-embolization (TACIE) combining TACE and local delivery of immune adjuvant (TLR9 agonist CpG oligodeoxynucleotide) is successfully performed using CpG-loaded Dox-PF127-LPD. Concurrent and safe local delivery of CpG and TACE during TACIE demonstrate leveraged TACE-induced immunogenic tumor microenvironment and augment systemic anti-tumor immunity in syngeneic N1S1 HCC rat model. Finally, the broad utility and enhanced therapeutic efficacy of TACIE are validated in the diethylnitrosamine-induced rat HCC model. TACIE using clinically established protocols and materials shall be a convenient and powerful therapeutic approach that can be translated to patients with HCC. The robust anti-cancer immunity and tumor regression of TACIE, along with its favorable safety profile, indicate its potential as a novel localized combination immunotherapy for HCC treatment.
CRISPR Editing Takes Aim at Ischemia/Reperfusion Injury
Authors: Oscar E. Reyes Gaido, Mark E. Anderson
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Historical Routes for Diversification of Domesticated Chickpea Inferred from Landrace Genomics
Authors: Anna A Igolkina, Nina V Noujdina, Margarita Vishnyakova, Travis Longcore, Eric von Wettberg, Sergey V Nuzhdin, Maria G Samsonova
Journal: Molecular Biology and Evolution (2023)

According to archaeological records, chickpea (Cicer arietinum) was first domesticated in the Fertile Crescent about 10,000 years BP. Its subsequent diversification in Middle East, South Asia, Ethiopia, and the Western Mediterranean, however, remains obscure and cannot be resolved using only archeological and historical evidence. Moreover, chickpea has two market types: "desi" and "kabuli," for which the geographic origin is a matter of debate. To decipher chickpea history, we took the genetic data from 421 chickpea landraces unaffected by the green revolution and tested complex historical hypotheses of chickpea migration and admixture on two hierarchical spatial levels: within and between major regions of cultivation. For chickpea migration within regions, we developed popdisp, a Bayesian model of population dispersal from a regional representative center toward the sampling sites that considers geographical proximities between sites. This method confirmed that chickpea spreads within each geographical region along optimal geographical routes rather than by simple diffusion and estimated representative allele frequencies for each region. For chickpea migration between regions, we developed another model, migadmi, that takes allele frequencies of populations and evaluates multiple and nested admixture events. Applying this model to desi populations, we found both Indian and Middle Eastern traces in Ethiopian chickpea, suggesting the presence of a seaway from South Asia to Ethiopia. As for the origin of kabuli chickpeas, we found significant evidence for its origin from Turkey rather than Central Asia.
Zn<sub>2</sub>SiO<sub>4</sub> Bioceramic Attenuates Cardiac Remodeling after Myocardial Infarction
Authors: Yanxin Zhang, Xin Li, Zhaowenbin Zhang, Huili Li, Dongmin Chen, Yiren Jiao, Chen Fan, Zhen Zeng, Jiang Chang, Yuhong Xu, Baowei Peng, Chen Yang, Yumei Que
Journal: Advanced Healthcare Materials (2023)

In the pursuit of therapeutic strategies for myocardial infarction (MI), a pivotal objective lies in the concurrent restoration of blood perfusion and reduction of cardiomyocyte apoptosis. However, achieving these dual goals simultaneously presents a considerable challenge. In this study, a Zn2 SiO4 bioceramic capable of concurrently sustaining the release of bioactive SiO32- and Zn2+ ions, which exhibit a synergistic impact on endothelial cell angiogenesis promotion, cardiomyocyte apoptosis inhibition, and myocardial mitochondrial protection against oxygen-free radical (reactive oxygen species) induced injury is developed. Furthermore, in vivo outcomes from a murine MI model demonstrate that either systemic administration via tail vein injection of Zn2 SiO4 extract or local application through intramyocardial injection of a Zn2 SiO4 composite hydrogel promotes cardiac function and reduces cardiac fibrosis, thus aiding myocardial repair. This research is the first to elucidate the advantageous effects of dual bioactive ions in myocardial protection and may offer a novel therapeutic avenue for ischemic heart disease based on meticulously engineered bioceramics.
The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis
Authors: Efthymia Kokkinou, Tea Soini, Ram Vinay Pandey, Aline van Acker, Jakob Theorell, Paulo Czarnewski, Egle Kvedaraite, Niels Vandamme, Magda Lourda, Chiara Sorini, Whitney Weigel, Anna Carrasco, Christopher Andrew Tibbitt, Heinrich Schlums, Ulrik Lindforss, Caroline Nordenvall, Malin Ljunggren, Maja Ideström, Mattias Svensson, Jan-Inge Henter, Eduardo J. Villablanca, Yenan T. Bryceson, Helena Rolandsdotter, Jenny Mjösberg
Journal: Cell Reports Medicine (2023)

Innate lymphoid cells (ILCs) are considered innate counterparts of adaptive T cells; however, their common and unique transcriptional signatures in pediatric inflammatory bowel disease (pIBD) are largely unknown. Here, we report a dysregulated colonic ILC composition in pIBD colitis that correlates with inflammatory activity, including accumulation of naive-like CD45RA+CD62L− ILCs. Weighted gene co-expression network analysis (WGCNA) reveals modules of genes that are shared or unique across innate and adaptive lymphocytes. Shared modules include genes associated with activation/tissue residency, naivety/quiescence, and antigen presentation. Lastly, nearest-neighbor-based analysis facilitates the identification of "most inflamed" and "least inflamed" lymphocytes in pIBD colon with unique transcriptional signatures. Our study reveals shared and unique transcriptional signatures of colonic ILCs and T cells in pIBD. We also provide insight into the transcriptional regulation of colonic inflammation, deepening our understanding of the potential mechanisms involved in pIBD.
Disentangling the Complex Web of Out-of-Hospital Cardiac Arrest Socioeconomic Disparities
Authors: Ryan Huebinger, Marina Del Rios
Journal: JAMA Network Open (2023)

Dong Hyun Choi, MD; Young Sun Ro, MD, DrPH; Jeong Ho Park, MD, PhD; Sun Young Lee, MD, PhD; Ki Jeong Hong, MD, PhD; Kyoung Jun Song, MD, PhD; Sang Do Shin, MD, PhD
Obesity and Gastrointestinal Cancer: A Life Course Perspective
Authors: Mengyao Shi, Yin Cao
Journal: JAMA Network Open (2023)

Gastrointestinal (GI) cancers account for about 27% of new cancer cases and 37% of cancer deaths globally, 1 with colorectal cancer (CRC) as the most common type in the United States. 2 Obesity (defined as body mass index [BMI] Ն30, where BMI is calculated as weight in kilograms divided by height in meters squared) has tripled in prevalence in the past several decades and is an established risk factor for multiple GI cancers, including esophageal adenocarcinoma, gastric cardia, liver, gallbladder, pancreatic, and colorectal cancer. 3However, most epidemiologic studies examined BMI
Monocyte heterogeneity in cardiovascular disease
Authors: Adele V Ruder, Suzan M W Wetzels, Lieve Temmerman, Erik A L Biessen, Pieter Goossens
Journal: Cardiovascular Research (2023)

Abstract Monocytes circulate the vasculature at steady state and are recruited to sites of inflammation where they differentiate into macrophages (MФ) to replenish tissue-resident MФ populations and engage in the development of cardiovascular disease (CVD). Monocytes display considerable heterogeneity, currently reflected by a nomenclature based on their expression of cluster of differentiation (CD) 14 and CD16, distinguishing CD14++CD16− classical (cMo), CD14++CD16+ intermediate (intMo) and CD14+CD16++ non-classical (ncMo) monocytes. Several reports point to shifted subset distributions in the context of CVD, with significant association of intMo numbers with atherosclerosis, myocardial infarction, and heart failure. However, clear indications of their causal involvement as well as their predictive value for CVD are lacking. As recent high-parameter cytometry and single-cell RNA sequencing (scRNA-Seq) studies suggest an even higher degree of heterogeneity, better understanding of the functionalities of these subsets is pivotal. Considering their high heterogeneity, surprisingly little is known about functional differences between MФ originating from monocytes belonging to different subsets, and implications thereof for CVD pathogenesis. This paper provides an overview of recent findings on monocyte heterogeneity in the context of homeostasis and disease as well as functional differences between the subsets and their potential to differentiate into MФ, focusing on their role in vessels and the heart. The emerging paradigm of monocyte heterogeneity transcending the current tripartite subset division argues for an updated nomenclature and functional studies to substantiate marker-based subdivision and to clarify subset-specific implications for CVD.
Oral prednisone regulates human skin T cells in delayed‐type hypersensitivity reaction elicited by diphencyprone
Authors: Heena Mehta, Carolyn Jack, Catherine Maari, Étienne Saint‐Cyr Proulx, Robert Bissonnette, Francisco Ramirez‐Valle, Marika Sarfati
Journal: Allergy (2023)

The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated.Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3+ T cell infiltrate, and examined the modulation by oral prednisone at single-cell level using multiparameter flow cytometry and unsupervised analysis.PPD was biased toward a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4+ CD25+ FoxP3+ regulatory T cells (Tregs), the minor CD4+ CD25+ FoxP3- ICOS+ PD-1+ (activated PD-1+ Th), and CD103+ tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8+ CD103+ CD25+ RoRγt+ PD-1+ ICOS+ IFNγ+ T cells (activated CD8+ IFNγ+ PD-1+ TRM). Oral prednisone decreased frequencies of activated PD-1+ Th and CD8+ IFNγ+ PD-1+ TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone.DTH and skin CD3+ T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD-1+ Th and CD8+ IFNγ+ PD-1+ TRM cells after DPCP exposure.
AGA Clinical Practice Update on Interventional EUS for Vascular Investigation and Therapy: Commentary
Authors: Marvin Ryou, John M. DeWitt, Koushik K. Das, Vanessa M. Shami
Journal: Clinical Gastroenterology and Hepatology (2023)

The purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound-guided vascular investigation and therapies.This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in endoscopic ultrasound-guided vascular investigation and therapy.